Specific chemical modification of bacterial type I dehydroquinase--opportunities for drug discovery.

Abstract

Type I dehydroquinase (DHQ1) is a class I aldolase enzyme that catalyzes the reversible dehydration of 3-dehydroquinic acid to form 3-dehydroshikimic acid by multistep mechanism that involves the formation of Schiff-base species. DHQ1 is present in plants and several bacterial sources but it does not have any counterpart in human cells. It has been suggested that DHQ1 may act as a virulence factor in vivo and therefore a promising target in the search for new antivirulence agents to combat widespread antibiotic resistance. This review covers recent progress in the structure-based design and chemical modifications caused by selective irreversible inhibitors. Computational studies aimed at understanding the experimentally obtained covalent modifications and inhibitory potencies of these inhibitors are also described.

• Authors: Concepción González-Bello
• Journal: Future medicinal chemistry (Future Med Chem) Vol. 7 Issue 17 Pg. 2371-83 ( 2015) ISSN: 1756-8927 [Electronic] England
• PMID: 26599605 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Review)

Chemical References

• Anti-Bacterial Agents
• Bacterial Proteins
• Hydro-Lyases
• 3-dehydroquinate dehydratase

Topics

• Anti-Bacterial Agents (chemistry, pharmacology)
• Bacteria (enzymology)
• Bacterial Proteins (antagonists & inhibitors, metabolism)
• Drug Discovery
• Drug Resistance, Bacterial (drug effects)
• Gram-Negative Bacteria (drug effects, physiology)
• Hydro-Lyases (antagonists & inhibitors, metabolism)
• Virulence (drug effects)